CRISPR Technology Shows Promise in Treating Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease affected patients may find hope in CRISPR-Cas9 gene editing technology. This gene therapy effectively knocked out the disease causing mutation in ALS model mice which had the human mutation and expanded their lifespan by 25 percent, shows a new study from the University of California, Berkeley. The onset of muscle wasting, a characteristic of the disease which proves to be fatal was delayed by the therapy. The findings are published in the journal Science Advances.

Amyotrophic Lateral Sclerosis (ALS)

  ALS is a progressive nervous system disorder that primarily affects motor neurons where the nerve cells gradually die. It is also called Lou Gehrig’s disease, after the baseball player who was diagnosed with it. It affects adults between the ages of 40 and 70. While the exact cause of the disease remains unknown, some cases are inherited. ALS usually begins muscle twitching weakness in a limb, or slurred speech. The effect of the disease on motor neurons limits the control one has on the muscles required to move, speak, eat and even breathe. Premature death of motor neurons in the brain and spinal cord which are crucial to control muscles cause the disease symptoms. The disease becomes fatal when the muscles that control breathing fail.

Study Overview

Laboratory mice were genetically engineered to contain the human gene mutations responsible for ALS. The mice expressed mutated genes that cause about 20 percent of all inherited forms and 2 percent of all case of ALS worldwide. "Being able to rescue motor neurons and motor neuron control over muscle function, especially the diaphragm, is critically important to being able to not only save patients, but also maintain their quality of life," said David Schaffer, a professor of chemical and biomolecular engineering and director of the Berkeley Stem Cell Center.

The research team used an adeno-associated virus to specifically seek out only motor neurons in the spinal cord and deliver the Cas9 gene into the nucleus of these cells. In the nucleus, the gene was translated into the Cas9 protein. The Cas9 protein acts as a pair of molecular scissors that cut and disable the mutant gene SOD1 (superoxide dismutase 1) responsible for ALS.

In mice treated with the CRISPR, the onset of the disease was delayed by five weeks. Moreover, treated mice lived about a month longer than the typical four-month lifespan of mice with ALS.

It was found after death that only the only the motor neurons that had the Cas9 protein in them had survived, others had died in the course of disease progression.

"The treatment did not make the ALS mice normal and it is not yet a cure," Schaffer cautioned. "But based upon what I think is a really strong proof of concept, CRISPR-Cas9 could be a therapeutic molecule for ALS. When we do additional optimization of the delivery to get CRISPR-Cas9 into an even higher percentage of cells, we think we are going to see even better increases in lifespan."

Reference:

1. Amyotrophic lateral sclerosis - (https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022)

Source-Medindia